ArticleCell reports2022
Mislocalization of protein kinase A drives pathology in Cushing's syndrome.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026Review
- The βBritish journal of pharmacology · 2026Article
- Acrodysostosis type 1: mechanisms explaining PRKAR1A mutation mediated dysregulation of cAMP-PKA signalling.Cell communication and signaling : CCS · 2026Review
- Review
- Genome-wide RNAi screening in C. elegans reveals OXPHOS and pyrimidine synthesis pathways as PKA regulators.Communications biology · 2025Article
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- The ascent of AKAPs, from architectural elements to kinase anchors: a perspective.The Biochemical journal · 2025Article
- The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants.The Journal of biological chemistry · 2025Article
- Hippo Signaling Is Essential for the Maintenance of Zona Glomerulosa Cell Fate in the Murine Adrenal Cortex.Endocrinology · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Article
- cAMP signaling: a remarkably regional affair.Trends in biochemical sciences · 2024Review
- The focal adhesion protein talin is a mechanically gated A-kinase anchoring protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hyperspectral imaging and dynamic region of interest tracking approaches to quantify localized cAMP signals.Biochemical Society transactions · 2024Review
- Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.Cell reports · 2024Article
- Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.Science advances · 2024Article
- Protein Kinase Structure and Dynamics: Role of the αC-β4 Loop.bioRxiv : the preprint server for biology · 2023Article
- Classification of Cushing's syndrome PKAc mutants based upon their ability to bind PKI.The Biochemical journal · 2023Article
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Mutations in the catalytic subunit of protein kinase A (PKAc) drive the stress hormone disorder adrenal Cushing's syndrome. We define mechanisms of action for the PKAc-L205R and W196R variants. Proximity proteomic techniques demonstrate that both Cushing's mutants are excluded from A kinase-anchoring protein (AKAP)-signaling islands, whereas live-cell photoactivation microscopy reveals that these kinase mutants indiscriminately diffuse throughout the cell. Only cAMP analog drugs that displace native PKAc from AKAPs enhance cortisol release. Rescue experiments that incorporate PKAc mutants into AKAP complexes abolish cortisol overproduction, indicating that kinase anchoring restores normal endocrine function. Analyses of adrenal-specific PKAc-W196R knockin mice and Cushing's syndrome patient tissue reveal defective signaling mechanisms of the disease. Surprisingly each Cushing's mutant engages a different mitogenic-signaling pathway, with upregulation of YAP/TAZ by PKAc-L205R and ERK kinase activation by PKAc-W196R. Thus, aberrant spatiotemporal regulation of each Cushing's variant promotes the transmission of distinct downstream pathogenic signals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.